The terms peri-menopausal refers to that time in a women's life between pre-menopause (the reproductive years) and post-menopause. This time period is usually between the ages of 40-60, but more often several years on either side of 50 years of age. This period is characterized by a rapid change in the hormonal balance in a woman. Although many different hormones are subject to rapid fluctuation during this time, the most notable are sex related hormones and in particular estrogens and to a lesser extent progestins. The cause of this fluctuation is the natural and time dependent cessation of ovian function. The hallmark of the ending of the peri-menopausal period and the beginning of the post-menopausal period is the cessation of ovian function or its inability to regulate the previously normal ovulation cycle in the woman. This cessation of function is clinically marked by the cessation of mensus of a period of one year or more. The time period over which this cessation of ovian function persists, i.e., the peri-menopausal time, is usually not a sudden or rapid event. The peri-menopausal state can last from a few months to more typically a year or more.
As mentioned before the peri-menopause is marked by fluctuations in the woman's hormonal composition, and these fluctuations are marked with many sequellae. Sometimes these sequellae pass without undo problems for the woman; however, they are often a source of moderate to severe discomfort and concern and are occasionally the source of pathological or even life-threatening events.
It is these sequellae in the peri-menopause time which define the syndrome. A list of common, through highly idiosyncratic, sequellae resulting from entering the peri-menopause are: Hot flashes and sweats, atrophic vaginitis, headache, dizziness, lack of concentration, irritability, loss of libido, joint pain, sleeplessness, apathy, lassitude, muscular weakness,-and palpitations. ("The Menopause", Ed. R. J. Beard, University of Park Press, 1976, Chapter 11). In addition, there has been described a "menopausal or peri-menopausal syndrome" marked with depression. Although there is some controversy as to whether this is a true psychiatric syndrome or not, the peri-menopause is a contributing factor. ("Harrison's principles of Internal Medicine", Ed. N. J. Isselbacher, et al., 9th ed., McGraw-Hill Book Co., 1980 pp. 1782-1783). In extreme cases, some of these sequellae in some women are pathological (such as fluid retention and imbalance) and even life-threatening, especially in those women predisposed to the effects of depression. However, for most women, a major cause of discomfort and concern lies not so much in the occurrence of one of more of these events, but the length of time which they must bear them and their unpredictable nature.
Since it would be unreasonable to believe that any treatment can turn back the course of aging, the clinical approach to the treatment of peri-menopausal syndrome has been one of amelioration. Specifically, the peri-menopausal woman in need of treatment is given a deescalating protocol of exogenous estrogen. This has the effect of bringing the patient slowly to the state of post-menopause, because although the exogenous estrogen effectively treats the symptoms of peri-menopause, it does not stop the inexorable decline in ovian function. Often, this de-escalation therapy requires a protracted period of time (as much as several years, in extreme cases) in order to allow the ovian function to cease by the time the exogenous estrogen is terminated. Although this therapy is effective and approved, it does carry many side-effects.
The side-effects usually associated with estrogen therapy are due not only to the estrogen, but also with the con-combinant progestins. In most cases, women with a uterus must be given estrogen and a progestin either together or more commonly in a cyclic protocol. The reason for this co-administration is to reduce the risk of endometrial cancer which estrogen given alone posses. The effects of the progestin are often poorly tolerated by many women, causing depression or even negating the salutory effects of the estrogen. The estrogen, itself, often causes unpleasant side-effects such as water retention, weight gain, hypertension, etc. The result is often non-compliance of the patient with the therapy and the subsequent suffering of the peri-menopausal symptoms.
Ideally, an improved therapy would be an agent which would ameliorate the symptoms of peri-menopausal syndrome, but would avoid or lessen the side-effects. Additionally, this ideal therapy would also reduce the period of time to bring the woman into a stable, post-menopausal state.